Joanne E. Brady

Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia

BACKGROUND: Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. METHODS: We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. RESULTS: On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20–2.93, CELF-E: aRR, 1.72; 95% CI, 1.12–2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13–2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40–4.17, and CPM aRR, 1.73; 95% CI, 1.04–2.88). CONCLUSIONS: Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.

Marijuana Use and Motor Vehicle Crashes

Since 1996, 16 states and the District of Columbia in the United States have enacted legislation to decriminalize marijuana for medical use. Although marijuana is the most commonly detected nonalcohol drug in drivers, its role in crash causation remains unsettled. To assess the association between marijuana use and crash risk, the authors performed a meta-analysis of 9 epidemiologic studies published in English in the past 2 decades identified through a systematic search of bibliographic databases. Estimated odds ratios relating marijuana use to crash risk reported in these studies ranged from 0.85 to 7.16. Pooled analysis based on the random-effects model yielded a summary odds ratio of 2.66 (95% confidence interval: 2.07, 3.41). Analysis of individual studies indicated that the heightened risk of crash involvement associated with marijuana use persisted after adjustment for confounding variables and that the risk of crash involvement increased in a dose-response fashion with the concentration of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol detected in the urine and the frequency of self-reported marijuana use. The results of this meta-analysis suggest that marijuana use by drivers is associated with a significantly increased risk of being involved in motor vehicle crashes.

Trends in Alcohol and Other Drugs Detected in Fatally Injured Drivers in the United States, 1999–2010

Drugged driving is a safety issue of increasing public concern. Using data from the Fatality Analysis Reporting System for 1999-2010, we assessed trends in alcohol and other drugs detected in drivers who were killed within 1 hour of a motor vehicle crash in 6 US states (California, Hawaii, Illinois, New Hampshire, Rhode Island, and West Virginia) that routinely performed toxicological testing on drivers involved in such crashes. Of the 23,591 drivers studied, 39.7% tested positive for alcohol and 24.8% for other drugs. During the study period, the prevalence of positive results for nonalcohol drugs rose from 16.6% in 1999 to 28.3% in 2010 (Z = -10.19, P < 0.0001), whereas the prevalence of positive results for alcohol remained stable. The most commonly detected nonalcohol drug was cannabinol, the prevalence of which increased from 4.2% in 1999 to 12.2% in 2010 (Z = -13.63, P < 0.0001). The increase in the prevalence of nonalcohol drugs was observed in all age groups and both sexes. These results indicate that nonalcohol drugs, particularly marijuana, are increasingly detected in fatally injured drivers.

Comparative analysis of outcome measures used in examining neurodevelopmental effects of early childhood anesthesia exposure

Introduction:Immature animals exposed to anesthesia display apoptotic neurodegeneration and neurobehavioral deficits. The safety of anesthetic agents in children has been evaluated using a variety of neurodevelopmental outcome measures with varied results. Methods:The authors used data from the Western Australian Pregnancy Cohort (Raine) Study to examine the association between exposure to anesthesia in children younger than 3 yr of age and three types of outcomes at age of 10 yr: neuropsychological testing, International Classification of Diseases, 9th Revision, Clinical Modification–coded clinical disorders, and academic achievement. The authors’ primary analysis was restricted to children with data for all outcomes and covariates from the total cohort of 2,868 children born from 1989 to 1992. The authors used a modified multivariable Poisson regression model to determine the adjusted association of anesthesia exposure with outcomes. Results:Of 781 children studied, 112 had anesthesia exposure. The incidence of deficit ranged from 5.1 to 7.8% in neuropsychological tests, 14.6 to 29.5% in International Classification of Diseases, 9th Revision, Clinical Modification–coded outcomes, and 4.2 to 11.8% in academic achievement tests. Compared with unexposed peers, exposed children had an increased risk of deficit in neuropsychological language assessments (Clinical Evaluation of Language Fundamentals Total Score: adjusted risk ratio, 2.47; 95% CI, 1.41 to 4.33, Clinical Evaluation of Language Fundamentals Receptive Language Score: adjusted risk ratio, 2.23; 95% CI, 1.19 to 4.18, and Clinical Evaluation of Language Fundamentals Expressive Language Score: adjusted risk ratio, 2.00; 95% CI, 1.08 to 3.68) and International Classification of Diseases, 9th Revision, Clinical Modification–coded language and cognitive disorders (adjusted risk ratio, 1.57; 95% CI, 1.18 to 2.10), but not academic achievement scores. Conclusions:When assessing cognition in children with early exposure to anesthesia, the results may depend on the outcome measure used. Neuropsychological and International Classification of Diseases, 9th Revision, Clinical Modification–coded clinical outcomes showed an increased risk of deficit in exposed children compared with that in unexposed children, whereas academic achievement scores did not. This may explain some of the variation in the literature and underscores the importance of the outcome measures when interpreting studies of cognitive function.

Trends in the Population Prevalence of People Who Inject Drugs in US Metropolitan Areas 1992-2007

Background People who inject drugs (PWID) have increased risk of morbidity and mortality. We update and present estimates and trends of the prevalence of current PWID and PWID subpopulations in 96 US metropolitan statistical areas (MSAs) for 1992–2007. Current estimates of PWID and PWID subpopulations will help target services and help to understand long-term health trends among PWID populations. Methodology We calculated the number of PWID in the US annually from 1992–2007 and apportioned estimates to MSAs using multiplier methods. We used four types of data indicating drug injection to allocate national annual totals to MSAs, creating four distinct series of component estimates of PWID in each MSA and year. The four component estimates are averaged to create the best estimate of PWID for each MSA and year. We estimated PWID prevalence rates for three subpopulations defined by gender, age, and race/ethnicity. We evaluated trends using multi-level polynomial models. Results PWID per 10,000 persons aged 15–64 years varied across MSAs from 31 to 345 in 1992 (median 104.4) to 34 to 324 in 2007 (median 91.5). Trend analysis indicates that this rate declined during the early period and then was relatively stable in 2002–2007. Overall prevalence rates for non-Hispanic black PWID increased in 2005 as compared to other racial/ethnic groups. Hispanic prevalence, in contrast, declined across time. Importantly, results show a worrisome trend in young PWID prevalence since HAART was initiated – the mean prevalence was 90 to 100 per 10,000 youth in 1992–1996, but increased to >120 PWID per 10,000 youth in 2006–2007. Conclusions Overall, PWID rates remained constant since 2002, but increased for two subpopulations: non-Hispanic black PWID and young PWID. Estimates of PWID are important for planning and evaluating public health programs to reduce harm among PWID and for understanding related trends in social and health outcomes.

Prevalence of Malignant Hyperthermia Due to Anesthesia in New York State, 2001-2005

BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic syndrome that variably expresses itself on exposure to triggering agents. MH prevalence in the United States is not well documented. In this study, we assessed the prevalence of MH in New York State hospitals. METHODS: Using New York hospital discharge data for the years 2001 through 2005, we identified all patients with a diagnosis of MH due to anesthesia using International Classification of Diseases, Ninth Revision, Clinical Modification code 995.86. MH prevalence was evaluated by demographic and clinical characteristics. RESULTS: Of the 12,749,125 discharges from New York hospitals during the study period, 73 patients had a recorded diagnosis of MH due to anesthesia. Nearly three quarters of the MH patients were male and 71% were patients from emergency/urgent admissions. The estimated prevalence rate of MH was 0.96 (95% confidence interval [CI] 0.67–1.24) per 100,000 surgical discharges and 1.08 (95% CI 0.75–1.41) per 100,000 discharges in which there was any indication of exposure to anesthesia. The estimated prevalence of MH for males was 2.5 to 4.5 times the rate for females. CONCLUSION: The prevalence of MH due to anesthesia in surgical patients treated in New York State hospitals is approximately 1 per 100,000. MH risk in males is significantly higher than in females.

Drug use and fatal motor vehicle crashes: A case-control study

Drugged driving is a serious safety concern, but its role in motor vehicle crashes has not been adequately studied. Using a case-control design, the authors assessed the association between drug use and fatal crash risk. Cases (n=737) were drivers who were involved in fatal motor vehicle crashes in the continental United States during specific time periods in 2007, and controls (n=7719) were participants of the 2007 National Roadside Survey of Alcohol and Drug Use by Drivers. Overall, 31.9% of the cases and 13.7% of the controls tested positive for at least one non-alcohol drug. The estimated odds ratios of fatal crash involvement associated with specific drug categories were 1.83 [95% confidence interval (CI): 1.39, 2.39] for marijuana, 3.03 (95% CI: 2.00, 4.48) for narcotics, 3.57 (95% CI: 2.63, 4.76) for stimulants, and 4.83 (95% CI: 3.18, 7.21) for depressants. Drivers who tested positive for both alcohol and drugs were at substantially heightened risk relative to those using neither alcohol nor drugs (Odds Ratio=23.24; 95% CI: 17.79, 30.28). These results indicate that drug use is associated with a significantly increased risk of fatal crash involvement, particularly when used in combination with alcohol.

Prescription Drug Monitoring and Dispensing of Prescription Opioids

Objective. In the United States, per-capita opioid dispensing has increased concurrently with analgesic-related mortality and morbidity since the 1990s. To deter diversion and abuse of controlled substances, most states have implemented electronic prescription drug monitoring programs (PDMPs). We evaluated the impact of state PDMPs on opioid dispensing. Methods. We acquired data on opioids dispensed in a given quarter of the year for each state and the District of Columbia from 1999 to 2008 from the Automation of Reports and Consolidated Orders System and converted them to morphine milligram equivalents (MMEs). We used multivariable linear regression modeling with generalized estimating equations to assess the effect of state PDMPs on per-capita dispensing of MMEs. Results. The annual MMEs dispensed per capita increased progressively until 2007 before stabilizing. Adjusting for temporal trends and demographic characteristics, implementation of state PDMPs was associated with a 3% decrease in MMEs dispensed per capita (p=0.68). The impact of PDMPs on MMEs dispensed per capita varied markedly by state, from a 66% decrease in Colorado to a 61% increase in Connecticut. Conclusions. Implementation of state PDMPs up to 2008 did not show a significant impact on per-capita opioids dispensed. To control the diversion and abuse of prescription drugs, state PDMPs may need to improve their usability, implement requirements for committee oversight of the PDMP, and increase data sharing with neighboring states.

Prevalence of alcohol and other drugs in fatally injured drivers.

AIM This study aims to examine the prevalence of alcohol and/or other drugs (AOD) in a large sample of fatally injured drivers. DESIGN Using data from the Fatality Analysis Reporting System for 2005-09, the authors examined the prevalence of AOD detected in fatally injured drivers in the United States. SETTING Fatal motor vehicle crashes occurring on public roads. PARTICIPANTS Drivers who died within 1 hour of the crash in 14 states that performed toxicological testing on more than 80% of these drivers. MEASUREMENTS The prevalence of AOD and multivariable-adjusted prevalence ratios (aPR). FINDINGS Of the 20,150 fatally injured drivers studied, 57.3% tested positive for AOD, including 19.9% being positive for two or more substances. Alcohol was the most commonly detected substance, present in 40.2% of the fatally injured drivers, followed by cannabinols (10.5%), stimulants (9.0%), narcotics (5.7%) and depressants (4.0%). Multivariable analysis revealed that AOD was significantly more prevalent among drivers who died in single-vehicle crashes [aPR 1.69, 95% confidence interval (CI): 1.62-1.76] or night-time crashes (aPR 1.43, 95% CI: 1.39-1.47), or who had a driving-while-intoxicated conviction within the past 3 years (aPR 1.41, 95% CI: 1.35-1.47), and less prevalent among drivers who were 65 years or older (aPR 0.45, 95% CI: 0.42-0.49), Asian (aPR 0.47, 95% CI 0.41-0.53) or female (aPR 0.88, 95% CI: 0.85-0.91) or who were operating a motor carrier (aPR 0.41, 95% CI 0.34-0.48). CONCLUSIONS More than half of fatally injured drivers in the United States had been using AOD and approximately 20% had been using polydrugs. The prevalence of AOD use varies significantly with driver and crash characteristics.

Intraoperative cardiac arrests in adults undergoing noncardiac surgery: incidence, risk factors, and survival outcome.

Background:Intraoperative cardiac arrest (ICA) is a rare but potentially catastrophic event. There is a paucity of recent epidemiological data on the incidence and risk factors for ICA. The objective of this study was to assess the incidence, risk factors, and survival outcome of ICAs in adults undergoing noncardiac surgery. Methods:The authors analyzed prospectively collected data for all noncardiac cases in the American College of Surgeons National Surgical Quality Improvement Program database from the years 2005 to 2007 (n = 362,767). Results:The incidence of ICA was 7.22 per 10,000 surgeries. After adjustment for American Society of Anesthesiologists physical status and other covariates, the odds of ICA increased progressively with the amount of transfusion (adjusted odds ratios = 2.51, 7.59, 11.40, and 29.68 for those receiving 1–3, 4–6, 7–9, and ≥ 10 units of erythrocytes, respectively). Other significant risk factors for ICA were emergency surgery (adjusted odds ratio = 2.04, 95% CI = 1.45–2.86) and being functionally dependent presurgery (adjusted odds ratio = 2.33, 95% CI = 1.69–3.22). Of the 262 patients with ICA, 116 (44.3%) died within 24 h, and 164 (62.6%) died within 30 days. Conclusions:Intraoperative blood loss as indicated by the amount of transfusion was the most important predictor of ICA. The urgency of surgery and the preoperative composite indicators of health such as American Society of Anesthesiologists status and functional status were other important risk factors. The high case fatality suggests that primary prevention might be the key to reducing mortality from ICA.